Ingestive decisions play a key role in a number of human conditions including obesity, diabetes, anorexia, hypertension, and coronary artery disease. The sense of taste is the most important factor in regulating these ingestive decisions, and therefore plays an important role in human health. Research conducted over the last few decades shows that taste centers in the brain have direct reciprocal connections with brain areas involved in homeostasis and ingestion. Taste has also been shown to engage the reward system, and dysfunction in this system may lead to overeating and obesity. However, the exact route whereby taste information engages reward and ingestive brain areas is unclear. The parabrachial nucleus (PBN) is a critical relay in the brainstem where gustatory information diverges via several ascending pathways to access forebrain sites involved in sensory discrimination, learning, intake and visceral processing, as well as reward. The studies of this proposal will test the hypotheses that a projection from the PBN to the ventral tegmental area (VTA) mediates taste-evoked reward, and a projection from the PBN to the lateral hypothalamus (LH) mediates taste-evoked ingestion. We will use a combination of complementary anatomical, physiological, and behavioral techniques to address this hypothesis. We propose the following specific aims: Aim 1: Functional organization of the gustatory PBN in mice. We will collect comprehensive normative data establish the organization of this key nucleus in wild type and taste-impaired mice. Aim 2: Does a direct projection from the PBN to the VTA mediate taste-evoked reward? This hypothesis will be first be evaluated with tract tracing and taste-evoked fos-like immunoreactivity (FLI) techniques: We will investigate whether or not VTA-projecting neurons are activated preferentially by sweet-tasting, rewarding stimuli in intact or taste-blind mice. We will also physiologically characterizing taste neurons that project to VTA using in vivo recording techniques. Finally, we will test the hypothesis that the VTA is essential for normal reward, but not taste function, by combining lesions of this area with behavioral analysis. In Aim 3, we will use a similar set of approaches to address the hypothesis that a direct projection from the PBN to the LH mediates taste-evoked ingestion, including tract tracing and taste-evoked FLI, in vivo physiology, and lesions of LH followed by measurement of behavior. We will utilize taste-blind trpm5 null mice in these experiments in order to separate effects of taste vs. post-ingestive feedback. PUBLIC HEALTH RELEVANCE: Ingestive decisions play a key role in a number of human conditions including obesity, diabetes, anorexia, hypertension, and coronary artery disease. The sense of taste is the most important factor in regulating these ingestive decisions, and therefore plays an important role in human health. The goal of this research is to elucidate pathways in the brain that link taste to feeding and reward.